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. 1985 Jul;52(1):73–80. doi: 10.1038/bjc.1985.151

Allostimulation of patients' lymphocytes generates both T and NK-like cells cytotoxic for autologous melanoma.

A Balsari, G Fossati, D Taramelli, G Tona, D Delia, R Giardini, G Parmiani
PMCID: PMC1977169  PMID: 3160380

Abstract

Killing of autologous melanoma (auto-Me) was obtained with pooled allostimulated peripheral blood lymphocytes (PBL) in 34/42 cases and found not to be due to a cross-reactivity between melanoma and allogeneic normal antigens. To see whether generation of tumour cytotoxic PBL by allostimulation was due to release of IL-2, PBL from 34 patients were divided into two aliquots and stimulated either by alloantigens or IL-2. Allostimulated PBL were cytotoxic for auto-Me in 30/34 cases (85%) whereas IL-2 generated tumour cytotoxic cells in 22/34 cases (64%). Lysis of K562, a target for monitoring NK-like activity, was obtained in 95-100% of cases with both stimuli. A similar frequency of OKT3+, OKT4+, OKT8+ and HNK1+ cells was found in PBL activated by allostimulation and IL-2, whereas a higher frequency of OKM1+ cells was evident in IL-2-stimulated PBL. Cold-target competition studies indicated that allostimulation generated at least two different types of effectors, one lytic to auto-Me but not to K562, and the other which lysed both targets. Allostimulated, FACS-separated T3- cells killed both auto-Me and K562 cells whereas T3+ cells lysed only auto-Me. It is concluded that allostimulation generated two subpopulations of auto-Me killer cells, one of the T lineage and the other NK-like, which both can destroy auto-Me targets.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Fossati G., Taramelli D., Balsari A., Bogdanovich G., Andreola S., Parmiani G. Primary but not metastatic human melanomas expressing DR antigens stimulate autologous lymphocytes. Int J Cancer. 1984 May 15;33(5):591–597. doi: 10.1002/ijc.2910330508. [DOI] [PubMed] [Google Scholar]
  2. Greenberg P. D., Cheever M. A., Fefer A. Definition of alien H-2 determinants on a Friend leukaemia by analysis of alloreactivity of CTL from primary MLC. J Immunogenet. 1981 Dec;8(6):493–508. doi: 10.1111/j.1744-313x.1981.tb00958.x. [DOI] [PubMed] [Google Scholar]
  3. Grimm E. A., Mazumder A., Zhang H. Z., Rosenberg S. A. Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes. J Exp Med. 1982 Jun 1;155(6):1823–1841. doi: 10.1084/jem.155.6.1823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Guerry D., 4th, Alexander M. A., Herlyn M. F., Zehngebot L. M., Mitchell K. F., Zmijewski C. M., Lusk E. J. HLA-DR histocompatibility leukocyte antigens permit cultured human melanoma cells from early but not advanced disease to stimulate autologous lymphocytes. J Clin Invest. 1984 Jan;73(1):267–271. doi: 10.1172/JCI111201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hurrell S. M., Zarling J. M. LY-2+ effectors cytotoxic for syngeneic tumor cells: generation by allogeneic stimulation and by supernatants from mixed leukocyte cultures. J Immunol. 1983 Aug;131(2):1017–1023. [PubMed] [Google Scholar]
  6. Kedar E., Schwartzbach M., Klein E. Expression of H-2b alloantigens in a variant of a Moloney virus-induced YAC (H-2a) lymphoma. Eur J Cancer Clin Oncol. 1982 Sep;18(9):861–865. doi: 10.1016/0277-5379(82)90196-1. [DOI] [PubMed] [Google Scholar]
  7. Knuth A., Danowski B., Oettgen H. F., Old L. J. T-cell-mediated cytotoxicity against autologous malignant melanoma: analysis with interleukin 2-dependent T-cell cultures. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3511–3515. doi: 10.1073/pnas.81.11.3511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lotze M. T., Grimm E. A., Mazumder A., Strausser J. L., Rosenberg S. A. Lysis of fresh and cultured autologous tumor by human lymphocytes cultured in T-cell growth factor. Cancer Res. 1981 Nov;41(11 Pt 1):4420–4425. [PubMed] [Google Scholar]
  9. López-Botet M., Silva A., Rodríguez J., de Landazuri M. O. Generation of T cell blasts with NK-like activity in human MLC: cellular precursors, IL 2 responsiveness, and phenotype expression. J Immunol. 1982 Sep;129(3):1109–1115. [PubMed] [Google Scholar]
  10. Macphail S., Paciucci P. A., Stutman O. Phenotypic heterogeneity of antisyngeneic tumor killer cells (ASTK) generated in allogeneic mixed lymphocyte reactions. J Immunol. 1984 Jun;132(6):3205–3210. [PubMed] [Google Scholar]
  11. Mazumder A., Grimm E. A., Rosenberg S. A. Lysis of fresh human solid tumor cells by autologous lymphocytes activated in vitro by allosensitization. Cancer Immunol Immunother. 1983;15(1):1–10. doi: 10.1007/BF00199454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Muul L. M., Gately M. K. Hydrocortisone suppresses the generation of nonspecific "anomalous" killers but not specific cytolytic T lymphocytes in human mixed lymphocyte-tumor cultures. J Immunol. 1984 Mar;132(3):1202–1207. [PubMed] [Google Scholar]
  13. Paciucci P. A., Macphail S., Zarling J. M., Bach F. H. Lysis of syngeneic solid tumor cells by alloantigen stimulated mouse T and non-T cells. J Immunol. 1980 Jan;124(1):370–375. [PubMed] [Google Scholar]
  14. Sensi M. L., Parenza M., Parmiani G. Alloreactivity and tumor antigens: generation of syngeneic antilymphoma killer lymphocytes by alloimmunization of mice with normal cells. J Natl Cancer Inst. 1983 Feb;70(2):291–297. [PubMed] [Google Scholar]
  15. Sensi M., Orosz C. G., Bach F. H. Alloantigen-induced cytotoxicity against syngeneic tumor cells: analysis at the clonal level. J Immunol. 1984 Jun;132(6):3218–3225. [PubMed] [Google Scholar]
  16. Strausser J. L., Mazumder A., Grimm E. A., Lotze M. T., Rosenberg S. A. Lysis of human solid tumors by autologous cells sensitized in vitro to alloantigens. J Immunol. 1981 Jul;127(1):266–271. [PubMed] [Google Scholar]
  17. Taramelli D., Fossati G., Balsari A., Marolda R., Parmiani G. The inhibition of lymphocyte stimulation by autologous human metastatic melanoma cells correlates with the expression of HLA-DR antigens on the tumor cells. Int J Cancer. 1984 Dec 15;34(6):797–806. doi: 10.1002/ijc.2910340610. [DOI] [PubMed] [Google Scholar]
  18. Taylor G. M., Bradley B. A. The role of allogeneic cells in the stimulation of cell-mediated cytotoxicity to leukaemia cells. A family study. Cancer Immunol Immunother. 1983;15(1):39–46. doi: 10.1007/BF00199460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Vose B. M., Bonnard G. D. Human tumour antigens defined by cytotoxicity and proliferative responses of cultured lymphoid cells. Nature. 1982 Mar 25;296(5855):359–361. doi: 10.1038/296359a0. [DOI] [PubMed] [Google Scholar]
  20. Vose B. M., White W. Tumour-reactive lymphocytes stimulated in mixed lymphocyte and tumour culture. Clonal analysis of effector cells in cytotoxic and proliferative assays. Cancer Immunol Immunother. 1983;15(3):227–236. doi: 10.1007/BF00199170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Vánky F., Gorsky T., Gorsky Y., Masucci M. G., Klein E. Lysis of tumor biopsy cells by autologous T lymphocytes activated in mixed cultures and propagated with T cell growth factor. J Exp Med. 1982 Jan 1;155(1):83–95. doi: 10.1084/jem.155.1.83. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Vánky F., Masucci M. G., Bejarano M. T., Klein E. Lysis of tumor biopsy cells by blood lymphocyte subsets of various densities. Autologous and allogeneic studies. Int J Cancer. 1984 Feb 15;33(2):185–192. doi: 10.1002/ijc.2910330206. [DOI] [PubMed] [Google Scholar]
  23. Zarling J. M., Bach F. H. Sensitization of lymphocytes against pooled allogeneic cells. I. Generation of cytotoxicity against autologous human lymphoblastoid cell lines. J Exp Med. 1978 May 1;147(5):1334–1340. doi: 10.1084/jem.147.5.1334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Zarling J. M., Robins H. I., Raich P. C., Bach F. H., Bach M. L. Generation of cytotoxic T lymphocytes to autologous human leukaemia cells by sensitisation to pooled allogeneic normal cells. Nature. 1978 Jul 20;274(5668):269–271. doi: 10.1038/274269a0. [DOI] [PubMed] [Google Scholar]
  25. de Vries J. E., Spits H. Cloned human cytotoxic T lymphocyte (CTL) lines reactive with autologous melanoma cells. I. In vitro generation, isolation, and analysis to phenotype and specificity. J Immunol. 1984 Jan;132(1):510–519. [PubMed] [Google Scholar]

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